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month download article/chapter n6-methyladenosine-dependent regulation subset-based association analysis jianbo tian & jiang chang national high-tech research pancreatic ductal adenocarcinoma crispr-cas9 essentiality screens top-notch young professionals long-range chromatin interactions spring-loaded base modification pathway-based meta-analysis dsrna-induced interferon response stage case–control study rna-seq analysis suggested full article pdf n6-methyladenosine modification heterogeneous nuclear ribonucleoprotein genome-wide screening brca gene expression eukaryotic messenger rna privacy choices/manage cookies pancreatic cancer risk dynamic reversible rna resectable pancreatic cancer regulates cancer growth messenger rna stability rna methylation independent population consisting mirna-mediated manner 3d genome browser article archives chromatin accessibility data rna recognition motif fto-dependent demethylation type ii diabetes distinguished young scholars article ying web-based browser rna biological processes confer higher risk functional genetic variants methylation modifications pancreatic adenocarcinoma regulatory dna tongji medical college jianbo tian article log c-myc mrna n6-methyladenosine single-nucleotide polymorphisms

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         headline:Identification of genetic variants in m6A modification genes associated with pancreatic cancer risk in the Chinese population
         description:N6-Methyladenosine (m6A) is the most prevalent modification of RNA in eukaryotes, and is associated with many cellular processes and even the development of cancers. We hypothesized that single-nucleotide polymorphisms (SNPs) in m6A modification genes, including its “writers”, “erasers” and “readers”, might affect the m6A functions and associate with the susceptibility to pancreatic ductal adenocarcinoma (PDAC). We first conducted a two-stage case–control study in Chinese population to interrogate all SNPs in 22 m6A modification genes. In the discovery stage, a total of 2735 SNPs were genotyped in 980 patients and 1991 controls. Then, the promising SNP was replicated in another independent population consisting of 858 cases and 2084 controls. As a result, we found the rs7495 in 3′UTR of hnRNPC was significantly associated with increased risk of PDAC in both stages (combined odds ratio = 1.22, 95% confidence interval = 1.12–1.32, P = 2.39 × 10–6). To further reveal the biological function of rs7495 and hnRNPC, we performed a series of biochemical experiments. Luciferase reporter assays indicated that rs7495G allele promoted hnRNPC expression through disrupting a putative binding site for has-miR-183-3p. Cell viability assay demonstrated that knockdown of hnRNPC suppressed the proliferation of PDAC cells. RNA-seq analysis suggested that as an m6A “reader”, hnRNPC played an important role in RNA biological processes. In conclusion, our findings elucidated that rs7495G could confer higher risk of PDAC via promoting the expression of hnRNPC through a miRNA-mediated manner. These results provided a novel insight into the critical role of m6A modification in tumorigenesis.
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      headline:Identification of genetic variants in m6A modification genes associated with pancreatic cancer risk in the Chinese population
      description:N6-Methyladenosine (m6A) is the most prevalent modification of RNA in eukaryotes, and is associated with many cellular processes and even the development of cancers. We hypothesized that single-nucleotide polymorphisms (SNPs) in m6A modification genes, including its “writers”, “erasers” and “readers”, might affect the m6A functions and associate with the susceptibility to pancreatic ductal adenocarcinoma (PDAC). We first conducted a two-stage case–control study in Chinese population to interrogate all SNPs in 22 m6A modification genes. In the discovery stage, a total of 2735 SNPs were genotyped in 980 patients and 1991 controls. Then, the promising SNP was replicated in another independent population consisting of 858 cases and 2084 controls. As a result, we found the rs7495 in 3′UTR of hnRNPC was significantly associated with increased risk of PDAC in both stages (combined odds ratio = 1.22, 95% confidence interval = 1.12–1.32, P = 2.39 × 10–6). To further reveal the biological function of rs7495 and hnRNPC, we performed a series of biochemical experiments. Luciferase reporter assays indicated that rs7495G allele promoted hnRNPC expression through disrupting a putative binding site for has-miR-183-3p. Cell viability assay demonstrated that knockdown of hnRNPC suppressed the proliferation of PDAC cells. RNA-seq analysis suggested that as an m6A “reader”, hnRNPC played an important role in RNA biological processes. In conclusion, our findings elucidated that rs7495G could confer higher risk of PDAC via promoting the expression of hnRNPC through a miRNA-mediated manner. These results provided a novel insight into the critical role of m6A modification in tumorigenesis.
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            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Xiaoyang Wang
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Haoxue Wang
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Heng He
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Bin Li
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Xiating Peng
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Danyi Zou
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Ying Zhu
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Rong Zhong
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Xiaoping Miao
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Jianbo Tian
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Jiang Chang
      url:http://orcid.org/0000-0001-8551-9458
      affiliation:
            name:Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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